Araştırma Çıktıları

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    Investigation of neuro-inflammatory parameters in a cuprizone induced mouse model of multiple sclerosis
    (TUBITAK SCIENTIFIC \& TECHNICAL RESEARCH COUNCIL TURKEY, 2021-01-01) Avsar, Timucin; Celikyapi Erdem, Gokce; Terzioglu, Gokhan; Tahir Turanli, Eda
    Cuprizone, copper chelator, treatment of mouse is a toxic model of multiple sclerosis (MS) in which oligodendrocyte death, demyelination and remyelination can be observed. Understanding T and B cell subset as well as their cytokines involved in MS pathogenesis still requires further scrutiny to better understand immune component of MS. The study presented here, aimed to evaluate relevant cytokines, lymphocytes, and gene expressions profiles during demyelination and remyelination in the cuprizone mouse model of MS. Eighty male C57BL/6J mice fed with 0.2\% cuprizone for eight weeks. Cuprizone has been removed from the diet in the following eight weeks. Cuprizone treated and control mice sacrificed biweekly, and corpus callosum of the brain was investigated by staining. Lymphocyte cells of mice analyzed by flow cytometry with CD3e, CD11b, CD19, CD80, CD86, CD4, CD25 and FOXP3 antibodies. IFNgamma, IL-1alpha, IL-2, IL-5, IL-6, IL-10, IL-17, TNF-alpha cytokines were analyzed in plasma samples. Neuregulin 1 (Nrg1), ciliary neurotrophic factor (Cntf) and C-X-C chemokine receptor type 4 (Cxcr4) gene expressions in corpus callosum sections of the mice brain were quantified. Histochemistry analysis showed that demyelination began at the fourth week of cuprizone administration and total demyelination occurred at the twelfth week in chronic model. Remyelination occurred at the fourth week of following withdrawal of cuprizone from diet. The level of mature and activated T cells, regulatory T cells, T helper cells and mature B cells increased during demyelination and decreased when cuprizone removed from diet. Further, both type 1 and type 2 cytokines together with the proinflammatory cytokines increased. The level of oligodendrocyte maturation and survival genes showed differential gene expression in parallel to that of demyelination and remyelination. In conclusion, for the first-time, involvement of both cellular immune response and antibody response as well as oligodendrocyte maturation and survival factors having role in demyelination and remyelination of cuprizone mouse model of MS have been shown.
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    Cumulative Corticosteroid Doses and Osteoporosis in Patients with Multiple Sclerosis
    (TURKISH LEAGUE AGAINST RHEUMATISM, 2010-01-01) Arslan, Sule; Celiker, Reyhan; Karabudak, Rana
    Objective: Multiple sclerosis (MS) is an inflammatory demyelinating disorder and corticosteroids used for the treatment of attacks are known to cause osteoporosis. Although osteoporosis is a known potential complication, many patients do not receive treatment to prevent bone loss. The aim of this study was to assess the relationship between cumulative doses of corticosteroids and bone mineral density (BMD) in MS patients. Materials and Methods: Twenty-two patients with MS (15 women, 7 men) and 22 age-and sex-matched subjects were enrolled into the study. Lumbar and femoral BMDs were measured using dual energy X-ray absorptiometry (DXA). Mobility and ambulation scales were also evaluated. Corticosteroid use was determined from an interviewer-administered questionnaire and patient records. Result: Lumbar and femoral BMDs were significantly lower in MS patients compared to the control group (p<0.05). 18.2\% of the MS patients had no restriction in activities of normal employment and domestic life when assessed with Kraft Mobility Scale. Only 22.7\% of the MS patients were fully ambulant when evaluated with Scranton Ambulation Scale. Cumulative dose was negatively correlated with lumbar BMD measurements (r=-0.505, p=0.017). Conclusion: Corticosteroids are an important part of the MS therapy and their use results in osteoporosis. Thus, cumulative corticosteroid dose should be determined and BMD measurements of the patients should be taken before treatment to determine those at high risk of osteoporosis, and preventive measures should be undertaken. (Turk J Rheumatol 2010